Omega-3-acid ethyl esters are a mixture of ethyl eicosapentaenoate and ethyl docosahexaenoate, which are ethyl esters of the omega−3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil. Together with dietary changes, they are used to treat high blood triglycerides which may reduce the risk of pancreatitis. They are generally less preferred than statins, and use is not recommended by NHS Scotland as the evidence does not support a decreased risk of heart disease. Omega-3-acid ethyl esters are taken by mouth.

Common side effects include burping, nausea, and an upset abdomen. Serious side effects may include liver problems and anaphylaxis. While use in pregnancy has not been well studied, some omega−3 fatty acids appear beneficial. How it works is not entirely clear.

Experts found a dose-dependent increase in the risk for atrial fibrillation in patients with cardiovascular diseases or cardiovascular risk factors who were being treated with omega-3-acid ethyl esters compared with those treated with placebo. The observed risk was at its highest at a dose of 4 g/d.[1]

Omega-3-acid ethyl ester medicines were approved for medical use in the European Union in 2000 and in the United States in 2004. Beyond the branded prescription formulation, it is also available as a generic medication and over the counter. In 2023, it was the 222nd most commonly prescribed medication in the United States, with more than 1 million prescriptions.

Omega-3-acid ethyl esters are used in addition to changes in diet to reduce triglyceride levels in adults with severe (≥ 500 mg/dL) hypertriglyceridemia. In the European Union and other major markets outside the US, omega-3-acid ethyl esters are indicated for hypertriglyceridemia by itself, or in combination with a statin for people with mixed dyslipidemia.

Intake of large doses (2.0 to 4.0 g/day) of long-chain omega−3 fatty acids as prescription drugs or dietary supplements are generally required to achieve significant (> 15%) lowering of triglycerides, and at those doses, the effects can be significant (from 20% to 35% and even up to 45% in individuals with levels greater than 500 mg/dL). It appears that both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglycerides, but DHA appears to raise LDL cholesterol more than EPA, while DHA raises HDL cholesterol while EPA does not.

Other omega−3 fish oil-based prescription drugs on the market have similar uses and mechanisms of action.

There are many fish oil dietary supplements on the market. There appears to be little difference in effect between dietary supplement and prescription forms of omega−3 fatty acids as to ability to lower triglycerides, but the ethyl ester products work less well when taken on an empty stomach or with a low-fat meal. The ingredients of dietary supplements are not as carefully controlled as prescription products and have not been tested in clinical trials as such drugs have. Prescription omega−3 products are more concentrated, requiring fewer softgels for the same daily dose. Dietary fish oil is often esterified and then molecularly distilled to attain higher purity and/or concentration. Typical 'concentrated' fish oil supplements have doubled contents of EPA/DHA (ca. 50-65%). There are also products on the market with even higher concentrations of EPA/DHA (ca. 65-85%), labelled with 'triple', 'ultra', or similar wording. Some producers also provide backward conversion of FAE to triglyceride form in assumption of its higher bioavailability, these products usually have 'rTG' in their names.